Geoduck clams have become the most profitable emerging fishery resource in Northwest Mexico, with profits of more than US$30 million during the last few years. The fishery targets two species—Panopea glohosa in the Gulf of California and Panopea generosa on the Pacific coast of Baja California—but is managed indistinctively. Despite its growing importance, scientific research on the basic biology of the Mexican stocks has been inexistent until recently. A major gap in knowledge is the interspecific distinction in structural and functional biological attributes. Consequently, the aim of this article is to provide the biological basis of phenotypic (morphometric) and genetic distinction between P. globosa and P. generosa to assist in their management and conservation. We found that P. generosa from the Pacific coast of Baja California is significantly smaller than P. glohosa from the northern Gulf of California in shell length, width, and height (t-tests, P < 0.0001), and that shell width and height scale differently to length in both species. Multivariate analyses (multidimensional scaling) provided additional support (stress = 0.04) to the species and geographical distinction. Genetic data from the nuclear ribosomal DNA provided contrasting results between polymerase chain reaction— restriction fragment length polymorphisms and direct sequencing. Ribosomal DNA sequences revealed higher diversity (haplotype and nucleotide) in P. glohosa. Standing in sharp contrast with the low intraspecific divergence, was the very large genetic differentiation between species in excess of 20% corrected Kimura 2-parameter sequence divergence and accounting for 98% of the molecular variance of both species. This differentiation was found to be of consequence for novel methods of molecular species identification and for the interpretation of the phylogeography and evolution of Panopea in the North Pacific. The relevance of our findings goes to the heart of filling a major information gap pertaining to the distinction of both species. Scientific and lay stakeholders of these valuable resources need to ascertain and acknowledge this distinction to adopt sustainable management and exploitation practices.